Dihydrofolate reductase purified from S. faecium and from beef liver will be studied by various techniques to elucidate the nature of the active site, the binding of ligands to that site and the identity of residues participating in the catalytic process. Methods of study will involve sequence determination, chemical modification, NMR and X-ray diffraction studies of crystalline complexes. BIBLIOGRAPHIC REFERENCE: A 13C Nuclear Magnetic Resonance Study of the Interaction of Ligands with Arginine Residues in Dihydrofolate Reductase. L. Cocco, R.L. Blakley, T.E. Walker, R.E. London and N.A. Matwiyoff. Biochem. Biophys. Res. Commun. 76, 183-188 (1977).